Chronic rejection occurs, in the lung, in the form of bronchiolitis obliterans
(BO), an inflammatory and fibroproliferative disease that leads to the obliteration of
the bronchioles. A concept of the pathogenesis of BO has been suggested and several
risk factors are associated to it, however, the exact etiology of this disease remains
unknown. Studies have suggested that an imbalance of leukotrienes (LT) over
prostaglandins (PG) promotes pulmonary fibrosis. The levels of LT and PG in the
human lung post-transplantation are unknown. We propose that an imbalance of
cysteinyl leukotrienes (CysLT) on PGE2 exists in the transplanted lung and may be
implicated in the pathogenesis of BO. We also suggest that leukotrienes contribute to
fibrosis through epithelial-mesenchymal transition (EMT). In order to test these
hypotheses, we have determined the levels of CysLTs and PGE2 in human
transplanted lung bronchoalveolar lavage fluid (BALf) samples and their clinical
correlations. We have also determined the capacity of CysLT to induce the
expression of EMT markers in vitro. We found high average levels of CysLT and
PGE2 in the BAL of transplant patients. A predominant peak of CysLT over PGE2
was observed at 52 weeks post-transplantation and two risk factors for BO, CMV
infections and Aspergillus were associated with CysLT/PGE2 ratio> 1. According to
our experimental parameters, CysLT can induce the repression of epithelial markers
but do not induce the expression of mesenchymal markers in vitro in small airway
epithelial cells.